WO2015117788A1 - Traitement de la theilériose bovine - Google Patents

Traitement de la theilériose bovine Download PDF

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Publication number
WO2015117788A1
WO2015117788A1 PCT/EP2015/050233 EP2015050233W WO2015117788A1 WO 2015117788 A1 WO2015117788 A1 WO 2015117788A1 EP 2015050233 W EP2015050233 W EP 2015050233W WO 2015117788 A1 WO2015117788 A1 WO 2015117788A1
Authority
WO
WIPO (PCT)
Prior art keywords
bolus
calves
buparvaquone
treatment
ecf
Prior art date
Application number
PCT/EP2015/050233
Other languages
English (en)
Inventor
Nicholas Mchardy
Original Assignee
Bimeda Amea Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bimeda Amea Limited filed Critical Bimeda Amea Limited
Priority to AP2016009355A priority Critical patent/AP2016009355A0/en
Publication of WO2015117788A1 publication Critical patent/WO2015117788A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0068—Rumen, e.g. rumen bolus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin

Definitions

  • ECF East Coast Fever
  • Theileriosis caused by the parasite Theilerice parva transmitted by the tick Rhipicephalus appendiculatus. It is a major disease of cattle in at least 11 countries in eastern, central and southern Africa. The affected countries include Burundi, Kenya, Malawi, Mozambique, Philippine, South Sudan, Africa, Kenya, Zaire, Zambia and clouds. Tropical theileriosis (TT) of cattle, caused by Theileria annulata and transmitted by several species of ticks, is equally severe. Affected countries include Morocco, Tunisia, Egypt, Sudan, Iran, Iraq, Iran, Pakistan, India and several other countries in Southern Europe, Southern Asia, Middle East and North Africa.
  • an intra-ruminal bolus for oral administration to a ruminant animal comprising buparvaquone in a bolus formulation.
  • the bolus comprises from 50 to 250 mg of buparvaquone.
  • the bolus may comprise approximately 100 mg of buparvaquone.
  • the bolus is dividable.
  • the bolus may comprise at least one groove for ease of division of the bolus.
  • the invention also provides a bolus comprising buparvaquone in an amount to deliver approximately 5 mg/Kg of the bodyweight of a ruminant.
  • the ruminant animal may be a bovine animal such as a calf.
  • the bolus of the invention is useful for the treatment of East Coast Fever and/or Tropical theileriosis.
  • bolus of the invention over all existing treatments for ECF and TT, all of which are solutions for intramuscular injection. These advantages apply particularly to calves, including very young calves.
  • Administration of a bolus by mouth is relatively easy, so it can be done by calf owners without the expense of a veterinarian or other animal health professional.
  • the bolus is simply placed over the back of the tongue, the mouth is held closed and the throat is stroked until the calf swallows the bolus.
  • the bolus contains 100 mg of buparvaquone (BPQ) - enough to treat a 20 Kg calf.
  • BPQ buparvaquone
  • the dose can be a multiple of boluses (or half boluses - the bolus is scored to make it easily broken in half), depending on the calf's weight. Calf owners know the approximate weight of their calves, so calculating the correct dose is easy. It is far easier than calculating the necessary dose of an injectable product, drawing it into the syringe and delivering it, without leakage or misplacement, by intramuscular injection.
  • a batch of 5,000 boluses was prepared by mixing, drying and blending the ingredients listed above. The mixture was formed into caplets using a tablet pressing technique. The uncoated caplets thus formed were light yellow coloured and elongated bioconvex in shape.
  • the disintegration time of the bolus in a medium simulating in vivo use was approximately 2 minutes.
  • the ingredients are present in the form of compressed powders or granules.
  • the bolus may be prepared by direct compression of the admixed ingredients.
  • a lubricant such as magnesium stearate after the granulation step.
  • the degree of compression will affect the hardness of the bolus.
  • Example 1 A trial was conducted to demonstrate the efficacy and safety of the dividable bolus of Example 1 for oral delivery, containing lOOmg of buparvaquone, and to indicate a likely dosage rate for the product under field conditions, for an effective and convenient product for the treatment of East Coast fever (ECF, Theileria parva infection) in calves, and by implication, also for the treatment of TT, Theileria annulata infection in calves.
  • ECF East Coast fever
  • TT Theileria annulata infection in calves.
  • test animals were high grade calves from a farm with no recent history of ECF. They were held in quarantine at the National Veterinary Research Centre (NVRC), Muguga, Kenya, for at least 14 days, to allow them to acclimatise and to ensure that they were free from disease and carrying no antibody to ECF. Antibody to ECF would indicate that they had experienced the disease in the past, and that they would be resistant to re-infection. They were kept housed and fed an appropriate high quality diet, including commercially available artificial milk substitute as appropriate. The calves were artificially infected with a dose of the Marikebuni stock of ECF that has been shown, over many years, to cause a consistent pattern of disease and to kill more than 90% of calves so infected in about 14-21 days after infection.
  • NVRC National Veterinary Research Centre
  • Cure is defined as the second consecutive day on which temperature remains below 39.5°C and theilerial schizonts are either absent from, or are clearly dying, in prescapular lymph node smears. This being a pilot study designed to indicate a likely effective dose rate for use in a more extensive field study in naturally-infected calves, it was terminated soon after the untreated calves had died, and the bolus-treated calves had either died or been cured, of their ECF infections.
  • the calves were housed on dry bedding in a closed tick-proof and rodent-free building with good ventilation. They were fed on good quality hay, commercially available milk replacement diet and concentrates, appropriate to their age.
  • the calves were infected, in compliance with the appropriate NVRC Standard Operating Procedure (SOP), by subcutaneous injection above the left prescapular lymph node with 1.0ml of a 1 in 10 dilution of the NVRC standard stabilate of the Marikebuni stock.
  • SOP Standard Operating Procedure
  • This infective dose has been shown, over many years, to result consistently in fatal ECF in more than 90% of susceptible cattle, usually within 14-21 days of infection. The day of infection was designated 'day 0' of the study. Observations
  • Lymph node smears Smears were prepared daily from the left prescapular lymph node (LPN) of all calves from day 7 and also from the right prescapular node (RPN) from day 10, in accordance with the NVRC SOP.
  • Blood smears Smears of ear- vein blood were prepared daily beginning two days after Theileria schizonts were first detected in lymph node smears. Theileria piroplasm parasitaemia was scored as percent of erythrocytes containing a piroplasm. Blood smears were also examined for the presence of other intra-erythrocytic parasites, i.e. Babesia bigemina and Anaplasma marginale.
  • Lymph node and blood smears were fixed with methanol and stained with Giemsa' s stain, then examined microscopically on the day that they were prepared, in accordance with the appropriate NVRC SOP. All microscope slides were identified by animal number, date of sampling and type of smear (e.g. LPN, RPN, B), but not the treatment group of the calf, so as to maintain "blinding" during microscopical examination.
  • Test substance and dosage The substance under test was the antitheilerial compound buparvaquone (BPQ) formulated as a pale yellow dividable bolus for oral administration. Each bolus contained lOOmg BPQ. Dosage rate was one bolus per 20 Kg body weight, equivalent to a nominal 5mg BPQ per Kg:-
  • BPQ antitheilerial compound buparvaquone
  • the calves were assigned to the three groups strictly in the order in which they attained "TS3" status - i.e. three days of temperature of 39.5°C or higher with Theileria schizonts present in lymph node smears.
  • the groups were:
  • Chronic cure is defined as occurring when rectal temperature has remained below 39.5°C for two consecutive days and schizonts are absent from lymph node smears, or present in very small numbers but clearly damaged by the treatment.
  • Score 0.5 indicates small number of drug-damaged or dead schizonts, of little or no pathological importance.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Feed For Specific Animals (AREA)

Abstract

Un bolus intra-ruminal pour l'administration par voie orale à un animal ruminant tel qu'un animal bovin, en particulier un veau, contient de la buparvaquone dans une formulation de bolus. Le bolus est utilisé pour traiter la theilériose bovine et la theilériose tropicale.
PCT/EP2015/050233 2014-02-06 2015-01-08 Traitement de la theilériose bovine WO2015117788A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AP2016009355A AP2016009355A0 (en) 2014-02-06 2015-01-08 Treatment of east coast fever

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14154171.4 2014-02-06
EP14154171.4A EP2905013B1 (fr) 2014-02-06 2014-02-06 Traitement de la fièvre de la côte orientale

Publications (1)

Publication Number Publication Date
WO2015117788A1 true WO2015117788A1 (fr) 2015-08-13

Family

ID=50068867

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2015/050233 WO2015117788A1 (fr) 2014-02-06 2015-01-08 Traitement de la theilériose bovine

Country Status (3)

Country Link
EP (1) EP2905013B1 (fr)
AP (1) AP2016009355A0 (fr)
WO (1) WO2015117788A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023553202A (ja) 2020-12-08 2023-12-20 ルミナント バイオテク コーポレーション リミテッド 動物に物質を送達するための装置および方法の改善

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GANTALA VENKATESH ET AL: "In vitro and in vivo evaluation of self-microemulsifying drug delivery system of buparvaquone", DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, vol. 36, no. 6, June 2010 (2010-06-01), pages 735 - 745, XP055123104, ISSN: 0363-9045, DOI: 10.3109/03639040903460446 *
MANTYLA A ET AL: "Design, synthesis and in vitro evaluation of novel water-soluble prodrugs of buparvaquone", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, ELSEVIER, AMSTERDAM, NL, vol. 23, no. 2, October 2004 (2004-10-01), pages 151 - 158, XP004580038, ISSN: 0928-0987, DOI: 10.1016/J.EJPS.2004.06.006 *
MURAGURI ET AL: "Clinical efficacy and plasma concentrations of two formulations of buparvaquone in cattle infected with East Coast fever (Theileria parva infection)", RESEARCH IN VETERINARY SCIENCE, BRITISH VETERINARY ASSOCIATION, LONDON, GB, vol. 81, no. 1, August 2006 (2006-08-01), pages 119 - 126, XP005315869, ISSN: 0034-5288, DOI: 10.1016/J.RVSC.2005.09.012 *

Also Published As

Publication number Publication date
AP2016009355A0 (en) 2016-08-31
EP2905013A1 (fr) 2015-08-12
EP2905013B1 (fr) 2016-08-03

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